Molecular and Cellular Neuroscience Commons^™

Regulation Of Akt And Wnt Signalling By The Dopamine D2 Receptor And Metabotropic Glutamate Receptor 2/3, Laurie P. Sutton

Electronic Thesis and Dissertation Repository

Akt and the Wnt pathway, two cascades that regulate GSK-3, have been implicated in schizophrenia and antipsychotic drug action. Although it is known that antipsychotic drugs alleviate psychosis by blocking the dopamine D2 receptor (D2DR) and that metabotropic glutamate receptor 2/3 (mGluR2/3) agonists may improve some of the symptoms of schizophrenia, it is unclear if both classes of drugs exert their effects through Akt, GSK-3 and/or the Wnt pathway or if changes in these pathways are mediated through the D2DR and mGluR2/3 respectively. In addition to antipsychotics, mood stabilizers and antidepressants also target GSK-3, suggesting that there must be something …

Characterizing And Treating The Neuropathology Of Tuberous Sclerosis Complex In The Mouse, Sharon W. Way

Dissertations & Theses (Open Access)

Tuberous sclerosis complex (TSC) is a multisystem, autosomal dominant disorder affecting approximately 1 in 6000 births. Developmental brain abnormalities cause substantial morbidity and mortality and often lead to neurological disease including epilepsy, cognitive disabilities, and autism. TSC is caused by inactivating mutations in either TSC1 or TSC2, whose protein products are known inhibitors of mTORC1, an important kinase regulating translation and cell growth. Nonetheless, neither the pathophysiology of the neurological manifestations of TSC nor the extent of mTORC1 involvement in the development of these lesions is known. Murine models would greatly advance the study of this debilitating disorder. This thesis …

Fibrinolytic Proteins And Brain-Derived Neurotrophic Factor Modulation Of Suprachiasmatic Nucleus Circadian Clock, Xiang Mou

Doctoral Dissertations

Mammalian circadian rhythms are controlled by a clock located in the suprachiasmatic nucleus (SCN). The mechanisms through which light phase-shifts the SCN circadian clock are similar to those underlying memory formation and long-term potentiation (LTP). Several secreted proteins, including tissue-type plasminogen activator (tPA), plasminogen, and brain-derived neurotrophic factor (BDNF), have been implicated in this process. These same proteins are important for photic phase-shifts of the SCN circadian clock. Early night glutamate application to SCN containing brain slices resets the circadian clock. Our experiments find that the endogenous tPA inhibitor, plasminogen activator inhibitor 1(PAI-1), blocked these shifts in slices from wildtype …

Presenilin Is Necessary For The Function Of Cbp In The Adult Drosophila Cns, Randy S. Boyles

UNLV Theses, Dissertations, Professional Papers, and Capstones

Dominant mutations in Presenilin (Psn) have been correlated with the formation of Aß- containing plaques in patients with inherited forms of Alzheimer's disease (AD). However, a clear mechanism directly linking amyloid plaques to the pathology of familial or sporadic forms of AD has remained elusive. Thus, recent discoveries of several new substrates for Psn protease activity have sparked alternative hypotheses to explain the preclinical symptoms of AD. CBP (CREB-binding protein) is a haplo- insufficient transcriptional co-activator with histone acetyltransferase (HAT) activity that has been proposed to be a downstream target for Psn signaling. Individuals with reduced CBP levels have cognitive …

Dopaminergic Innervation Of The Subventricular Zone In The Murine Brain, Linda Beth Drozdowicz

Honors Scholar Theses

The subventricular zone (SVZ) is one of two areas in the brain that, in a healthy mouse, continually generate neurons throughout adulthood. While it was previously thought that only the A9 neurons of the substantia nigra sent dopaminergic afferents to the SVZ, recent studies suggest that the A10 neurons of the ventral tegmental area may innervate this area. This project has aimed to discover which, if either, model is correct.

Examination of the Aphakia (AK) mouse was used to determine the role of distinct midbrain regions in SVZ regulation. Additionally, intraperitoneal injections of the chemical MPTP were used to deduce …

The Expression And Cellular Localization Of Cc-Chemokine Receptor 5 (Ccr5) After Traumatic Brain Injury, Vuvi H. Nguyen

Dissertations & Theses (Open Access)

Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of impact and damage can include scalp laceration, skull fraction, cerebral contusions and lacerations as well as intracranial hemorrhage. Following the initial insult, a delayed response occurs and is characterized by hypoxia, ischemia, cerebral edema, and infection. During secondary brain injury, a series of neuroinflammatory events are triggered that can produce additional damage but may also help to protect nervous tissue from invading pathogens and help to repair the damaged tissue. Brain microglia and astrocytes become …

Protein-Protein Interactions That Regulate Neurotransmitter Release From Retinal Ribbon Synapses, (Leigh) Beth T. Latham

Dissertations & Theses (Open Access)

Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses Photoreceptors and bipolar cells in the retina form specialized chemical synapses called ribbon synapses. This type of synapse differs physiologically from “conventional” chemical synapses. While “conventional” synapses exocytose neurotransmitter-filled vesicles in an all-or-none fashion in response to an action potential, a retinal ribbon synapse can release neurotransmitter tonically (sustained) in response to graded changes in membrane potential or phasically (transient) in response to a large change in membrane potential.

Synaptic vesicle exocytosis is a tightly controlled process involving many protein-protein interactions. Therefore, it is likely that the dissimilarity in the …

Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock

Dissertations & Theses (Open Access)

Mounting an effective response to tissue damage requires a concerted effort from a number of systems, including both the immune and nervous systems. Immune-responsive blood cells fight infection and clear debris from damaged tissues, and specialized pain receptors become hypersensitive to promote behavior that protects the damaged area while it heals. To uncover the cellular and molecular mechanisms underlying these processes, we have developed a genetically tractable invertebrate model of damage-induced inflammation and pain hypersensitivity using Drosophila larvae.

To study wound-induced inflammation, we generated transgenic larvae with fluorescent epidermal cells and blood cells (hemocytes). Using live imaging, we monitored the …

Signaling Mechanisms That Control Gap Junctional Coupling Between Retinal Neurons, Wade Kothmann

Dissertations & Theses (Open Access)

Gap junctions between neurons form the structural substrate for electrical synapses. Connexin 36 (Cx36, and its non-mammalian ortholog connexin 35) is the major neuronal gap junction protein in the central nervous system (CNS), and contributes to several important neuronal functions including neuronal synchronization, signal averaging, network oscillations, and motor learning. Connexin 36 is strongly expressed in the retina, where it is an obligatory component of the high-sensitivity rod photoreceptor pathway. A fundamental requirement of the retina is to adapt to broadly varying inputs in order to maintain a dynamic range of signaling output. Modulation of the strength of electrical coupling …

The Expression And Cellular Localization Of Cc-Chemokine Receptor 5 (Ccr5) After Traumatic Brain Injury, Vuvi H. Nguyen

Dissertations & Theses (Open Access)

Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of impact and damage can include scalp laceration, skull fraction, cerebral contusions and lacerations as well as intracranial hemorrhage. Following the initial insult, a delayed response occurs and is characterized by hypoxia, ischemia, cerebral edema, and infection. During secondary brain injury, a series of neuroinflammatory events are triggered that can produce additional damage but may also help to protect nervous tissue from invading pathogens and help to repair the damaged tissue. Brain microglia and astrocytes become …

Developmental Changes In The Structure And Composition Of The Postsynaptic Density, Matthew T. Swulius

Dissertations & Theses (Open Access)

The development of the brain and its underlying circuitry is dependent on the formation of trillions of chemical synapses, which are highly specialized contacts that regulate the flow of information from one neuron to the next. It is through these synaptic connections that neurons wire together into networks capable of performing specific tasks, and activity-dependent changes in their structural and physiological state is one way that the brain is thought to adapt and store information. At the ultrastructural level, developmental and activity-dependent changes in the size and shape of dendritic spines have been well documented, and it is widely believed …

Genes Involved In Mushroom Body Development And Behavior In Drosophila, Christine Nicole Serway

UNLV Theses, Dissertations, Professional Papers, and Capstones

Mushroom bodies (MBs) are the site of multi modal sensory integration critical for associative conditioning in Drosophila. They have been central to research on the structure function relationship in the brain for over one hundred years due to their unique shape and readily accessible physiology. This dissertation incorporates three different approaches to further elucidate the genetic and molecular nature of this structure function relationship.

First, the suite of genetic and molecular tools available in Drosophila melanogaster, facilitated the molecular mapping of a 25-year old MB structural mutant called mushroom body miniature B (mbmB) to the gene Pendulin [Pen, also known …

Metastability And Plasticity In A Conceptual Model Of Neurons, Bo Deng

Department of Mathematics: Faculty Publications

For a new class of neuron models we demonstrate here that typical membrane action potentials and spike-bursts are only transient states but appear to be asymptotically stable; and yet such metastable states are plastic — being able to dynamically change from one action potential to another with different pulse frequencies and from one spike-burst to another with different spike-per-burst numbers. The pulse and spike-burst frequencies change with individual ions’ pump currents while their corresponding metastable-plastic states maintain the same transmembrane voltage and current profiles in range. It is also demonstrated that the plasticity requires two one-way ion pumps operating in …